This proposed research plan describes a 3 year training program for the development of an academic career. The candidate has completed four years of post-doctoral fellowship training and will expand her training during this time period to progress to an academic position. This proposal will define the role of resistin in obesity-related insulin resistance. Mitchell A. Lazar, M.D., Ph.D. will mentor the applicant's scientific development. Dr. Lazar is a recognized leader in the field of nuclear receptors and adipogenesis. Dr. Lazar is the Chief of Endocrinology, Metabolism and Diabetes and the Director of the Penn Diabetes Center. To enhance the training, the applicant will enlist the expertise of Morris Birnbaum, M.D., Ph.D., Howard Hughes Professor and Rexford Ahima, M.D., Ph.D., assistant professor and Director of the Physiology Core of the Penn Diabetes Center. In addition to performing research, the Principal Investigator will benefit from lectures, seminars, and advisory committee meetings. The proposed research will focus on a newly identified hormone that is secreted from adipocytes and which has been shown to antagonize the effects of insulin. The proposed experiments will entail analyzing components in the insulin signaling cascade downstream of insulin binding to determine the mechanism of antagonism of insulin action by resistin (Specific Aim 1). In order to address the role of resistin in insulin resistance associated with obesity (Specific Aim 2), we will study the in vivo regulation of resistin in several different animal models of obesity. We plan to study obesity models in which leptin signaling is impaired (ob/ob, db/db) and intact (Agouti, Cpe-fat). The proposed research plan will reveal detailed information about resistin's role in obesity and diabetes. The scientific environment of the University of Pennsylvania provides the ideal opportunity for the candidate to develop her career by executing the proposed research while utilizing the expertise and resources of Dr. Mitchell A. Lazar. Such an environment should allow the candidate to maximize her potential to establish herself as an independent investigator.